ROSMAP-Compass: A data-harmonised, AI-ready atlas of 22 million single nuclei from the ROSMAP cohort

The Religious Orders Study and Memory and Aging Project (ROSMAP) cohort has generated the world's most comprehensive single-cell transcriptomic resource for Alzheimer's disease research. Naturally, in a project spanning multiple years with dozens of research groups involved, the resulting data landscape shows fragmentation across sequencing chemistries, protocols, and pipelines. This presents both a challenge and a unique opportunity for harmonized, collaborative analysis. Following an early data integration strategy and complete realignment of all single nucleus RNA sequencing data, we generated a fully harmonized resource: ROSMAP-Compass, comprising more than 22 million high-quality nuclei from 2,058 donors in multiple brain regions from the ROSMAP and Neuro Psychiatric Symptoms (NPS-AD) cohorts. Through systematic curation and unified reprocessing, we addressed substantial technical challenges including chemistry-specific biases, cross-study batch effects, and sample redundancies across multiple studies spanning different time periods and research groups. ROSMAP-Compass demonstrates the critical importance of systematic data harmonization when integrating large-scale single-cell datasets from multiple sources. By combining open science principles with cutting-edge AI integration, we provide both a critical resource for understanding Alzheimer's disease heterogeneity and a blueprint for making complex biomedical data accessible to the global research community. The full resource, interactive web portal, and LLM compatible API are freely available, empowering researchers worldwide to accelerate discovery in neurodegenerative diseases.